The cariostatic efficacy of fluoride present in communal water supplies is well-known and has resulted in the widespread use of fluoride in this manner, as well as in a variety of other delivery systems, for the prevention of dental caries. It is also known that the ingestion of excessive amounts of fluoride during the childhood period of tooth formation may result in the development of dental fluorosis. Additional reports have indicated that the presence of nutritional inadequacies serves to increase both the prevalence and severity of dental fluorosis and may also contribute to the development of skeletal fluorosis. However, virtually no information exists from human studies regarding the impact of nutritional inadequacies on any other possible pharmacologic or genotoxic effects of fluoride. In view of the widespread use of fluoride as well as the existence of nutritional inadequacies throughout the world, additional information is needed to permit and assure the safe public health use of fluoride for caries prevention. The long-term objective of this investigation is to provide necessary information to permit and assure the safe public health use of fluoride to prevent caries. The specific objectives of this investigation are to determine: (1) the relationship between chronic nutritional inadequacies and the prevalence/severity of dental and skeletal fluorosis associated with excessive fluoride ingestion; and (2) if nutritional inadequacies exacerbate any pharmacologic or genotoxic effects of fluoride in persons having chronic, excessive fluoride exposure. The investigation will involve population groups in The People's Republic of China and in Ecuador who have various combinations of nutritional inadequacies and fluoride exposure of varying degrees from either drinking water or ambient air. Collected data will include dental fluorosis and caries prevalence, nutritional status, skeletal fluorosis, fluoride content of urine and blood, and extensive chemical, electrolyte, and lymphocyte SCE assays of blood. The results of these studies will be useful in developing or refining current guidelines regarding the safe public health use of fluoride.